A common problem encountered when treating female infertility is abnormal hormone levels, particularly, abnormally high luteinizing hormone (LH) and/or androgen levels, and often low follicle stimulating hormone (FSH) levels. This is especially true with patients suffering from polycystic ovarian disease (PCOD).
To induce ovulation and achieve a successful pregnancy in PCOD patients various treatments have been attempted. Excellent results have been obtained by administering essentially pure FSH, which has been found to correct the LH:FSH imbalance (METRODIN-The Gonadotropins in the Polycystic Ovarian Disease, product brochure of The Ares-Serono Group, 1990). It has also been suggested to administer a GnRH agonist (Hoe 766) to suppress endogenous gonadotropin (FSH/LH) secretion by a down-regulation mechanism and, while maintaining such suppression, administer a conventional gonadotropin treatment regimen to induce ovulation. (Coutts, Excerpta-Medica Int'l Congress Series 652:608, 1984). While not directed to treating PCOD, U.S. Pat. No. 4,845,077 suggests that the individual variability in response to gonadotropin therapy can be eliminated by cojointly administering a GnRH antagonist with the gonadotropin treatment.
A new generation of highly active GnRH antagonists are disclosed in WO 89/01944. While a large number of active decapeptides are disclosed in this publication, one of them has been tested more extensively than the others. This decapeptide has been named Antide and is represented by the formula N--Ac--D--2--Nal--D--pClPhe--D--3---Pal--Ser--NicLys--D--NicLys--Leu--ILys --Pro--D--Ala--NH.sub.2. Antide has been shown to provide profound long-term inhibition of tonic gonadotropin (FSH/LH) levels in ovariectomized monkeys, the duration of such inhibition being dose dependent (Leal et al, J. Clin. Endocrinol. Metab. 67:1325, 1988). More recently, it was discovered that ovariectomized monkeys treated with Antide would respond to a large i.v. bolus of gonadotropin releasing hormone (GnRH) by showing a transient increase in gonadotropin levels which subsequently fell back to the inhibited state (Leal et al, Contraception 40:623, 1989).